With proper configuration, spybot is very powerful and wont just throw up a large number of pop ups. You can set certain variables and block certain pieces of the registry from even being edited in any fashion, such as preventing program installs and such.
I run spybot S&D, AVG antivirus/spyware, lava ad aware, and malwarebyte's anti malware. no problems hardly, though the few times I had a problems was when trying to run spyware and ad aware at the same time, they conflict with each other if both are performing a scan at the same time. Other than that, It kills most viruses before they run, and the few that do run, they are blocked from doing any damage and are automatically deleted upon reboot.
EDIT also, if you just run spybot to update it for example, and it throws up a bunch of stuff, thats because the user isnt commiting an effort well enough. I scan weekly and if Im downloading a bunch of shit in a day, I defrag and clean my files up, scan, then download a few things, scan again, then reboot, and scan again. YOu gotta be hardcore on that shit to keep your computer safe.